Mercapto quinoline n-oxides and their use in combatting dandruff

ABSTRACT

Novel compounds having the structural formula in tautomeric form:   AND METAL SALTS AND COMPLEXES THEREOF WHEREIN R1 and R2 are hydrogen, alkyl, cycloalkyl, aryl, alkylthio, halogen, nitro, trifluoromethyl or alkoxy; x is an integer from 1 to 4 and y is an integer from 1 to 2. The invention also includes anti-dandruff shampoos containing the above metal salts and complexes and to a method of combatting dandruff comprising applying to the hair and scalp a detergent composition containing the above metal complexes.

United States Patent [191 Furia et al.

[451 Jan. 21, 1975 MERCAPTO QUINOLINE N-OXIDES AND THEIR USE IN COMBATTING DANDRUFF [75] Inventors: Thomas E. Furia, l-lartsdale; David H. Steinberg, Bronx, both of NY.

[73] Assignee: Ciba-Geigy Corporation, Ardsley,

[22] Filed: Jan. 22, 1973 [21] Appl. No.: 325,712

Related US. Application Data [62] Division of Ser. No. 842,377, July 16, 1969, Pat. No.

[52] US. Cl 260/270 R, 252/106, 252/107, 260/45.75, 260/45.8, 260/283 S, 260/283 Bl, 424/245, 424/258 Primary Examiner-Donald G. Daus Assistant ExaminerD. Wheeler [57] ABSTRACT Novel compounds having the structural formula in tautomeric form:

( 1 x zl I OH and metal salts and complexes thereof wherein R and R are hydrogen, alkyl, cycloalkyl, aryl, alkylthio, halogen, nitro, trifluoromethyl or alkoxy; x is an integer from 1 to 4 and y is an integer from 1 to 2. The invention also includes anti-dandruff shampoos containing the above metal salts and complexes and to a method of combatting dandruff comprising applying to the hair and scalp a detergent composition containing the above metal complexes.

4 Claims, No Drawings 1 MERCAPTO QUINOLINE N-OXIDES AND THEIR USE IN COMBATTING DANDRUFF This is a divisional of application Ser. No. 842,377, filed on July 16, 1969, now US. Pat. No. 3,723,435.

BACKGROUND OF THE INVENTION The present invention relates to novel mercapto quinoline N-oxides, metal complexes thereof and the utilization of the latter in anti-dandruff shampoo compositions and in methods for combatting dandruff.

The precise cause of dandruff in the scalp area is at present unknown. It has been theorized that the skin particles normally shed from the scalp surfaces during the process of aging accumulate and combine with the oils exuded by the scalp to form a condition which enhances the growth of those bacteria, fungi, or other biological agents responsible for the propagation and accumulation of dandruff.

It is emphasized, however, that the above mechanism is at best an unproven theory. One of the major obstacles to a complete acceptance of this theory is the fact that many extremely powerful bactericides and fungicides have no effect whatsoever on the spread of dandruff in the human scalp. Moreover, substances such as elemental sulfur which are not recognized as having potent bactericidal and fungicidal activity are extremely effective in the control of dandruff. Obviously, then, factors other than bacteria and fungi contribute to the growth and spread of dandruff.

Accordingly, the selection of agents suitable for the control of dandruff is necessarily a hit and miss proposition. It is only by the process of trial and error that those skilled in the art have been able to provide the art with effective anti-dandruff agents to date.

One type of such anti-dandruff agent is described in US. Pat. No. 3,236,733. The compounds described therein as being useful for combatting dandruff are certain metal salts or complexes of 1-hydroxy-2- pyridinothione. Although providing a high degree of anti-dandruff activity, the metal salts of 1-hydroxy-2- pyridinethiones suffer from the disadvantage that they are slightly toxic, particularly when applied to the scalps of those individuals having unusually sensitive skin. Such individuals experience irritation and reddening of the skin and in certain cases, highly aggravated reactions in the form of open sores, etc., upon application of these thione salts to their scalps.

There exists in the prior art, therefore, the need for an anit-dandruff agent which is highly effective in combatting dandruff and, simultaneously, non-toxic to the scalp or skin.

Accordingly, it is an object of the present invention to provide novel chemical compounds having a high degree of anti-dandruff activity which are non-toxic to the skin or scalp.

It is further object of the present invention to provide an anti-dandruff shampoo composition which is nontoxic to the scalp or skin.

2 It is still a further object of the present invention to provide a method for combatting dandruff with a composition which is non-toxic to the scalp or skin.

SUMMARY OF THE INVEN'IION The above and other objects of the present invention are achieved by the provision of novel mercapto quinoline N-oxides having the following structural formula in tautomeric form:

and salts and complexes thereof with metals non-toxic to the scalp or skin wherein R and R are independently selected from the group consisting of hydrogen, alkyl of l to 24 carbon atoms, cycloalkyl, aryl, alkylthio having 1 to 24 carbon atoms, halogen, nitro, trifluoromethyl and alkoxy of 1 to 4 carbon atoms; x is an integer from 1 to 4 and y is an integer from 1 to 2.

It has been found that metal complexes of theabove mercapto quinoline N-oxides possess a high degree of anit-dandruff activity and are relatively non-toxic to the scalp and skin.

Shampoos containing the above-described mercapto quinoline N-oxide metal complexes and methods involving the application thereof to the scalp and hair have been found to be highly effective in controlling the propagation and spread of dandruff. At the same time, the application of these shampoo compositions to the scalp produce no toxic effects thereon, even in individuals having extremely sensitive skin.

DETAILED DESCRIPTION OF THE INVENTION In the above tautomeric structural formula, R and R have been defined as hydrogen, alkyl, cycloalkyl, aryl, alkylthio, halogen, nitro, trifluoromethyl and alkoxy.

The preferred mercapto quinoline N-oxides are those wherein R and R are each H.

Among the alkyl substituents, the most preferred are the lower alkyl groups, i.e. having 1 to 4 carbon atoms, e.g. methyl, ethyl, n-propyl, iso-propyl, butyl. Higher alkyl substituents include by way of example dodecyl, tetradecyl, hexadecyl, octadecyl, eicosyl, docosyl, tetracosyl.

Suitable cycloalkyl substituents include by way of example cyclopentyl, methylcyclopentyl, ethylcyclopentyl, etc; chlorocyclopentyl, dichlorocyclopentyl, cyclohexyl, methylcyclohexyl, ethylcyclohexyl, etc., chlorocyclohexyl, dichlorocyclohexyl.

Exemplary of the aryl substituents are phenyl, o-tolyl,

dichlorophenyl, etc.

Suitable alkyl groups of the alkylthio and alkoxy substituents include those mentioned above; the most preferred being the lower alkyl groups.

Suitable halogen substituents include trifluoromethyl, fluoro, chloro, bromo and iodo; the most preferred being chloro.

Salts or complexes of the above described mercapto quinoline N-oxides with any metal which is non-toxic to the scalp or skin may be employed in the present invention. Suitable metals include lithium, sodium, potassium, zinc, calcium, tin, copper, antimony, lead. manganese, and aluminum.

The preferred metals are sodium and zinc; zinc being the most preferred. The most preferred anti-dandruff agent is the zinc complex of 2-mercapto-quinoline-N- oxide.

The terms salts or complexes have been employed to define the metal derivatives of the 2mercaptoquinoline-N-oxides of the present invention, the specific compound formed being determined by the valence of the metal M. The structure may be depicted thusly:

contacting with a per-acid such as per-maleic acid in a suitable solvent.

The intermediate 2-chloro-quinoline-N-oxide (11) may be converted to the 2-mercapto-quinoline-N-oxide (111) or directly to the metal salt or complex thereof (IV). The mercapto compound may be obtained by reacting the chloro derivative with a mixture of NaSH and Na s in the presence of an acid.

Optionally, the metal salt or complex may be prepared directly by reacting the chloro derivative with MSH in the presence of a proton acceptor solvent. It is to be understood that mixtures of complexes of various metals with 2-mercapto-quinoline-Noxide may be prepared by reacting the chloro derivative with a mixture of metal salts. Moreover, the metal complexes may be converted to complexes of other metals by reaction with salts of metals which are lower on the EMF scale.

Also, the mercapto-quinoline-N-oxides (llI) may be converted to the metal complex (IV) by reaction with the appropriate metal salt.

The antidandruff agents of the present invention may be incorporated in any of the shampoo compositions well known in the prior art. Generally, shampoo (R1 compositions compriseaqueous detergent bases in liq- X 2 uid or paste form containing conventlonal shampoo adw ditives such as coloring agents, perfume, fillers, thickeners, solvents, opacifiers, builders, conditioning S M agents such as amine oxide surfactants, lanolin derivaf tives, preservatives, buffers, anti-static agents, etc. The

O n shampoos generally contain from about 1 to about 30 wherein R R x and y have the meanings given above; M is a metal and n is the valence of said metal.

The compounds of the present invention may be prepared according to methods well known in the prior art. Generally, the following reaction scheme may be employed to prepare the compounds of the invention:

percent by weight of a detergent.

The detergents may be anionic, cationic, amphoteric or non-ionic. Suitable anionic detergents include by way of example propylated naphthalenesulfonic acid, sodium alkylnaphthalenesulfonate, sulfonated monoglyceride of coconut fatty acids, sodium oleyl sulfate.

Suitable examples of cationic detergents include lauryltrimethylammonium chloride, cetyltrimethylam- III The starting materials (1) are well known in the prior art. They are described, e.g. in: C. A.,- vol. 54, pp. 24741 and 24742; C. A., vol. 55, p. 18728; C. A., vol. 51, p 1959; C. A., vol. 44, p. 632; C. A., vol. 41, p

2056; C. A., vol. 57, p 11832; C. A., vol. 58, p 13913; 65

C. A., vol. 58, p 13744; C. A., vol. 59, pp. 8743 and 97432; J. A. C. 8., vol. 64, p 1357.

The starting materials (I) are converted to the N oxides by methods well known in the prior art, e.g. by

monium bromide, cetyldimethylethylammonium bromide.

Suitable amphoteric detergents include N-alkyl taurines, such as N-dodeeyl taurine, alkyl a-alanines such as dodecyl B-alanine, long chain alkyl amino sulfonic acids, alkyl sulfonamides and the like.

Among the non-ionic detergents which may be employed in the shampoo compositions of the present invention may be mentioned by way of example polyethylene glycol lauryl ether, polyethylene esters of fatty acids or rosin acids, polyethylene glycol stearate, sorbitan monopalmitate, sorbitan monooleate.

The anti-dandruff agents of the present invention may be incorporated in the above shampoo compositions in amounts sufficient to provide effective antidandruff control on the hair and scalp. Generally, amounts ranging from about 0.1 to about 10 percent by weight are included.

It has been found that the anti-dandruff agents of the present invention are highly substantive to the scalp and hair, ie., is retained on the scalp and in the hair despite rinsing and builds up a layer thereof on the scalp and in the hair upon repeated use. By applying the above shampoos to the scalp and hair, the propagation and spread of dandruff may be effectively controlled.

Because of their microbiological activity, the salts and complexes of the present invention may be beneficially soaps; into other products where antibacterial or fungicidal activity is desired such as antibacterial and deodorant toilet soaps, including detergents and combinations of detergents and soaaps; laundry detergents and soaps; other laundry finishing compositions such as softeners. acid sours, antichlors and both natural and synthetic starches; in hard surface disinfecting compositions such as floor and wall cleaners; various personal products such as creams, powders, tales and aerosol sprays; in water treatment, secondary oil recovery and heat exchanges, polymers such as plasticized polyvinyl chloride and the like for the prevention of microbiocidal deterioration; and in paints and coatings in both oil base and latex types or in can preservation and in improving weatherability.

The following non-limiting examples are illustrative of methods for the preparation of the anti-dandruff agents of the invention.

EXAMPLE 1 a. 420 g of maleic anhydride was dissolved in 900 ml of chloroform and cooled. 84 g of 30 percent hydrogen peroxide was added dropwise thereto with stirring in an ice bath. The mixture was stirred at -5C for 12 hours. 49.2 g of 2-chloroquinoline in 90 ml of chloroform was added dropwise thereto with stirring in an ice bath at 0-5C over 1.5 hours. The resulting mixture was stirred overnight at 0-5C and stored at 5C. for days. The mixture was then filtered, yielding 479.1 g of a precipitate having an melting point of l4l-5. The filtrate was stripped to yield 99.7 g of residue which was dissolved in chloroform and passed through a bed of 2100 g of neutral alumina and eluted with chloroform. 12 X 200 ml fractions were obtained followed by 12 X 450 ml fractions. The product fractions (8-14) were combined and stripped to yield 28.0 g of residue. The residue was placed in a freezer and previously prepared seeds were added which induced solidification of the product. A sample of the purified product was dried to constant weight at 55/0.1 mm. It had a melting point of 848 and gave satisfactory elemental analysis.

Analysis for C H ONCL:

Cale: C, 60.18; H, 3.36; N, 7.80; Cl, 19.73.

Found: C, 60.40; H, 3.85; N, 7.88; Cl, 20.01

C, 60.14; H, 3.71; H, 7.86.

b. 840 g of maleic anhydride was dissolved in 1,800 ml of chloroform at 40-50C and the mixture transferred to a 3,000 ml, 3-neck flask equipped with a stirrer, condenser, thermometer and dropper funnel. While cooling in an ice-bath, 168 g of hydrogen peroxide (30%) was added to the mixture dropwise over 1.5 hours. While maintaining the temperature of the mixture at 5-10C, 88.4 g of 2-chloroquinoline (dissolved in 250 ml of chloroform) was added thereto dropwise with stirring over 1 hour. The reaction was continued with stirring for 3 hours at 5-l0C. The reaction mixture was transferred to a refrigerator and stored for 6 days.

The precipitate was filtered from the reaction mixture and washed with chloroform to yield 910 g of insoluble material. The filt 'rate was placed in a 4-liter separatory funnel and washed with 1,000 ml of a 10 percent solution of potassium carbonate. The wash solution was separated therefrom and the filtrate again washed with 500 ml of a 10 percent potassium carbonate solution. The product contained in the chloroform layer was separated and placed in a refrigerator over solid potassium carbonate to dry overnight.

The chloroform solution was then passed through a layer of neutral alumina on a sintered glass funnel under light suction to remove potassiumcarbonate and water. A clear chloroform solution was obtained. The alumina was washed with 200 cc of chloroform and combined with the original filtrate. The combined solutions were stripped on a rotary evaporator keeping the temperature below 40C. to yield a dark colored syrupy residue. The residue was treated with 250 ml of anhydrous ethyl ether. The resulting mixture was shaken with ml of water for 5 minutes to yield a copious light colored precipitate. The mixture was cooled to 5l0C and filtered. The precipitate was washed with 200 ml of water followed by washing with 200 m1 of ethyl ether. The precipitate was then dried over phosphorous pentoxide in a dessicator, under vacuum for 5 days to yield 48.7 g (51.4 percent yield) of product having a melting point of 77-84C. Comparison by thin layer chromatography using silica gel (absorbent), 4:1 benzene-methanol (developer) and iodine (detector) indicated identity with the previously prepared product.

EXAMPLE 2 Preparation of 2-Mercapto-Quinoline-N-Oxide 30.5 g of 2-chloro-quinoline-N-oxide and 850 ml of water were added to a 2-liter flask equipped with a stirrer, condenser, thermometer and dropping funnel. The mixture was heated with stirring to 45C. 5.8 g of sodium hydrosulfide (50 percent assay) and 41.7 g of sodium sulfide (32.5 percent assay) in ml of water were added to the dropping funnel and added dropwise over 2 hours, to the contents of the flask while heating at 65C for 45 minutes. The reaction mixture which was completely in solution was cooled to room temperature. A solution of 70 g of concentrated hydrochloric acid in 70 ml of water was placed in a dropping funnel and added dropwise to the reaction mixture with stirring. Hydrogen sulfide evolved from the reaction mixture was collected in a 20% NaOH trap. After 1 hour sufficient hydrochloric acid solution was added to bring the pH of the reaction mixture to 1.0. The copious precipitate deposited from the reaction mixture was filtered on a sintered glass funnel, washed with 700 ml of water and dried overnight under vacuum. The product weighed 19.0 g (63.2% yield), had a melting point of 6567C. and was identified by infrared spectroscopy to be 2-mercapto-quinoline-N-oxide.

Using procedures analogous to those of this example employing equivalent amounts of the appropriate starting materials, other compounds falling within the scope of the present invention are readily prepared.

EXAMPLE 3 k Preparation of the Sodium Complex of 2-Mercapto-Quinoline-N-Oxide a. A mixture of 1.8 g of 2-chloro-quinoline-N-oxide, 1.1 g of sodium hydrosulfide and ml of dimethylformamide was heated on a steam bath for 1 hour and 10 allowed to stand overnight. The reaction mixture was stripped to dryness to remove dimethylformamide. Approximately 25 ml of ethyl alcohol was added and the mixture filtered to remove a small amount of a white precipitate of NaCl. The filtrate was stripped and gave 2.3 g residue. This residue (R1) was triturated with benzene which left a new residue (R2) of 1.0 g having a melting point of 235-250. This was recrystallized from a mixture of acetone (60 ml) and heptane (60 ml) and afforded 0.8 g of product. After drying overnight at 65/().2 mm, it had a melting point of 255260 (dec.). A neutral equivalent established that the product was the sodium salt of 2-mercapto-quinoline-N- oxide.

EXAMPLE 4 Preparation of Zinc Complex of 2-Mercapto-Quinoline-N-Oxide a. 1.5 g of 2-mercapto-quinoline-N-oxide, 0.68 g of 50% NaOH solution and 20 ml of water were mixed and vigorously stirred. The insoluble matter was filtered off. The filtrate was back-titrated with dilute hydrochloric acid to a pH of 9.0. With continuous vigorous stirring a solution of 1.26 g of zinc chloride in 20 ml of water was added dropwise to the filtrate to give a copious light green-yellow precipitate. The precipitate was collected by filtration, washed twice with 30 ml portions of water, once with 20 ml of ethanol and once with 20 ml of anhydrous ethyl ether. The precipitate of the zinc complex of 2-mercapto-quinoline-N- oxide was then dried under vacuum at 56C at 2 mm for 2 hours to give 1.7 g (96.2 percent yield) having a melting point of 243-46 (dec.).

b. 17.7 g of 2-mercapt0-quinolineN-oxide was added portion wise over /2 hour to 8.8 g of sodium hydroxide in 250 ml of water with stirring to yield a mixture having a pH of 12. The insoluble matter was filtered off and the filtrate back-titrated with dilute HCl to a pH of 9.09.5. A solution of 13.63 g of zinc chloride in 200 ml of water was added portionwise to the filtrate with vigorous stirring to give a copious precipitate of the zinc complex of 2-mercapto-quinoline-N-oxide. The product was filtered and washed twice with 200 ml of water, once with 200 ml of ethanol and once with 200 ml of anhydrous ethyl ether. The product was dried under vacuum (2mm) over phosphorous pentoxide for;

17 hours to give 19.6 g (94 percent yield); melting point 24446.

Analysis for:

Calc.: C, 51.74; H, 2.90; S, 15.35; N, 6.71; Zn, 15.65.

Found: C, 51.26; H, 3.00; S, 14.46; N, 6.56; Zn, 15.76

C, 51.28; H, 2.93; S, N, 6.67; Zn, 15.80.

c. A clear solution of 68.1 mg zinc chloride in 10 ml of water was added to a clear solution of 199 mg of the sodium complex of 2-mercapto-quinoline-N-oxide in 5 ml of water with swirling. The resulting tan precipitate was filtered, washed successively with 3 X ml portions of water, 2 X 15 ml portions of ethanol and 2 X 15 ml portions of anhydrous ethyl ether. The zinc complex product was air dried, then dried to constant weight at at 0.1 mm. This afforded 170 mg of product having a melting point of 250(dec.).

d. A clear solution of 1.02 g of zinc chloride in ml of water was added to a clear solution of 3.32 g of the sodium complex of 2-mercapto-quinoline-N-oxide in 100 ml of water with stirring. After 15 minutes of stirring, the resulting precipitate of the zinc complex of 2-mercapto-quinoline-N-oxide was filtered, washed successively with 3 X 50 ml portions of water, 4 X 25 ml portions of ethanol and 6 X 25 ml portions of anhydrous ethyl ether, and air dried. The product (2.8 g 90 percent yield) had a melting point of 250-260 (dec.). Following drying in a vacuum oven at 90-10010.3 mm for 2 hours, the product had a melting point of 240250(dec.).

Analysis for:

Calc.: N, 6.70; S, 15.34; Zn, 15.64.

Found: N, 6.58; S, 1461:0033 Zn, l5.53i0.23.

The foregoing procedures are employed to prepare salts or complexes of the other metals (M) listed above.

As stated above, the 2-mercapto-quinoline-N-oxide metal complexes of the present invention have an effectiveness against dandruff comparable to that of the metal complexes of the hydroxy-pyridinethiones of US. Pat. No. 3,236,733 but are comparatively less toxic to the scalp and skin.

The following examples illustrate the effectiveness of the compositions of the invention in controlling dandruff.

EXAMPLE 6 The microbiological activities of the zinc and sodium complexes of 2-mercapto-quinoline-N-oxide (MONO) against P. Ovale were compared with the sodium and zinc salts of pyridinethione-N-oxide (PTO) and other conventional soapbacteriostats. P. Ovale is a microorganism associated with dandruff conditions.

Equal amounts of the respective compounds were dissolved in methyl cellosolve, dimethylformamide, or water, serially diluted in ten fold sequence and incorporated into plates of molten Agar. The plates were allowed to solidify, were then inoculated with P. Ovale (ATCC 14521 incubated at 2 7C. for 4 daysand inspected for growth. The results are set forth in Table I.

TABLE 1 Activity of Various Antimicrobial Agents Against P. Ovale TABLE l-Continued Activity of Various Antimicrobial Agents 10, October, 1961. 0.3 g of shampoo was applied in each instance to 12.5 sq. in. of calf skin (equivalent to Compounds Against P. Ovale C in PPM 3.5 g of shampoo per 90.2 sq. in. of human scalp) and Na]kybdimethybethybbemw ammonium a rich lather workedup for 2 minutes. The calf skin was cyclohexyl sulfamate t000 5 then rinsed in running tap water for 30 seconds with s y y P yp vigorous massage to remove all lather. The moist skin of woo was then given a second lather identical to the first and Diiodohydrotryquinoline 1000 again rinsed as before. After air drying, the calf skins ig' f m' sg ig 688 were cut into 2.1 cm discs and placed on agar inocu- Undecen-l-ol i000 to lated with P. Ovale. After 4 days incubation at 27C,

g 4 the zones of inhibition size were recorded. The results 7 Minimum Inhibitory Concentration are set forth in Tabl It is apparent from the results of Table 1 that the ac.- apparen g these r.es.ults g substgmmty tivity of the compositions of the present invention are an acuvlty O t e composmons O t e l are Comparable to that of the pyridinethione N oxides of? comparable to those of the agents described in U.S. U.S. Pat. No. 3,236,733. It is also apparent that the 3236731 Should be noted imaner other conventional bacteriostats, fungistats and quater- Zone slzeproduced by ZHMQNO mdlcate a nary ammonium compounds are totally void of activity 1523322? i gg gig g ifg zgfgggg f g g a inc gg vastly Inferior to the compositions of the mven 20 ZnMONO is less soluble than ZnPTO it would be expected to exhibit a smaller zone size. EXAMPLE 7 The following example illustrates the antimicrobial The substantivity/activity of the Zinc complex of spectrum of the compositions of the invention as com- 2-mercapto-quinoline'N-oxide of the invention in calfpared Wlth those of 3,236,733 skin were compared with the zinc salt of pyridineth- EXAMPLE 8 ione-N-oxide in the following manner. ZnMQNO and ZnPTO were incorporated by blending on a 3-ro1l mill Equlvalem amounts Of QM Q NaMQNO, in amounts of 1% and 2% by weight into a non-bacteri- ZnPTO and NaPTQ were methyl Cello ostatic paste shampoo of the following composition. Solve (PTO) d dlmethy] formamlde (MONO) Ten fold serial dilutions were prepared employing additional solvent and equal aliquots pipetted into molten Long chain modified alkanolamide, anionic 25.4% (50C) agar support di N i A was Laurie acid 11.9% Coconut ulkanoiamidg nonnunic 19% ployed for all bacteria and Mycological Agar was em- Triethanolamine Salt of lauwyl f 19% ployed for the fungi and dermatophyte. After preparing thylenedmmme 11% pour plates for the bacteria and streaks for the fungi Water 57.8% and dermatophyte, the plates were incubated (37C 100-0% and 27C, respectively) and observed for growth. The

results are set forth in Table 3.

Calf skin specially prepared by the hod O Vinson As is apparent from these results, zinc and sodium IN VITRO TESTS FOR MEAS I ANTIBACTE- 40 PTO may be classed as broad-spectrum antimicrobial RIAL ACTIVITY OF TOILET SOAP AND DETER- agents showing good activity at low concentrations GENT BARS by L. J. Vinson, E. L. Ambye, A. G. Benagainst Gram-positive and negative bacteria, fungi and net, Journal of Pharmaceutical Sciences, Vol. 50, P. dermatophytes.

Table 2 Replicate Zone of Inhibition Against P. Ovale Calf Skin Plates 2% Zinc PTO) 2% MQNOZ 1 Application 2 Applications 1 Application 2 Applications "Zinc pyridienthione-N-oxidc from commercial Head and Shoulders shampoo 'Zinc l mcrcaptoquinolinc-N-oxide from formulated paste shampoo as described in Example 6.

T. interdigiiale "l'hc strains of Staph. (IMH'UA and I1. (u/i employed are the official test organisms used in AA'ICC Iest Mcllmd -10651.

* lmli'ux viilgarir N20 is a strong ammonia producer and employed by many organizations to test lrculcd diapers ""Asprrgi'llm urvmi' llllHi is employed lty iniluslry and the US. Army to test the degradation of pninl films ing in the 11 S and included ivy the USDA for testing What is claimed is: s, phenyl, phenyl substituted with chlorine or methyl, 1. A compound selected from the group consisting of halogen, trifluoromethyl and alkoxy of one to four carcompounds having the following structural formula in atoms; and wherein the metal is Selected m lithtautorneric form: ium, sodium, potassium, calcium.

2. A compound as claimed in claim I wherein R, and

[ (1 UX] (1 2 U R are hydrogen,

3. Metal complexes of a compound having the fol lowing structural formula in tautomeric form:

O OH

wherein the metal is selected from lithium, sodium, po-

OH tassium, calcium. and metal salts and complexes thereof wherein R, and comPound according to Claim 3 whfiein Said R are each independently selected from the group metal 15 Sodlum consisting of hydrogen, alkyl of one to 24 carbon atom- 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS HAVING THE FOLLOWING STRUCTURAL FORMULA IN TAUTOMERIC FORM:
 2. A compound as claimed in claim 1 wherein R1 and R2 are hydrogen.
 3. Metal complexes of a compound having the following structural formula in tautomeric form:
 4. A compound according to claim 3 wherein said metal is sodium. 